MEDICINE MAN: Actor Sean Connery once portrayed a scientist hunting for a cure for cancer in the Amazon.
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In the 1992 film Medicine Man, actor Sean Connery stars as a grizzled scientist who discovers a cure for cancer in the Amazon and then struggles to replicate his findings as bulldozers destroy the very forests that harbor it. "What don't you understand?" he wails. "I found the cure for the...plague of the 20th century, and now I've lost it!"
If Connery reprised that role today, his enemy might instead be Big Pharma, whose working methods have staunched the pipeline for medicines derived from nature. The advent of high-throughput screening technologies has allowed companies to test 100,000 compounds per day for specific biological functions, but that speed comes at a price: Drug approval rates are far lower for synthetic compounds than those derived from natural products, which, due to their complexity, are harder to screen.
"I believe this is bad in the long term for both the pharmaceutical companies and the public," says John Vederas of the University of Alberta. "The current balance between high-throughput screening of synthetic libraries and pursuit of natural-product leads is skewed in an unfavorable way."
In this week's Science, Vederas and his student Jesse Li explain that this shift from natural products, along with tighter safety requirements and a focus on blockbuster drugs, is a key reason why the pharmaceutical pipeline is drying up. Today, just over 100 nature-derived drugs are currently in clinical trials, a 30 percent decline from just a few years ago.
The problem with current screening technologies is that compounds found in plants, animals and microbes have more complicated structures than those in synthetic chemical libraries, leading to challenges in their isolation, identification and manufacture. Moreover, natural compounds are often present at such low levels that they cannot be readily tested using current automated technologies. Finally, drugmakers exploring the natural world face the risk of isolating and identifying a known compound that cannot be patented.
Even so, there's a bright side to the story. Vederas believes that this trend could be turned around by automating the hunt for natural compounds. For instance, it may soon be possible to automatically separate all of the chemicals in an organism, identify them, and catalogue them in a library for future screening. He also advocates "smart screening" methods, such as using engineered E. coli in assays that help weed out common antibiotics produced by soil microbes to speed the search for new ones.
Whether or not all this novel technology means that Sean Connery, er, "Dr. Robert Campbell," will make a more credible scientist in the future, it's still worth taking a look at some of the greatest hits from nature's medicine cabinet.
[Slide show: Nature-Based Pharmaceuticals]
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7 Comments
Add Comment"...it may soon be possible to automatically separate all of the chemicals in an organism..." Is that really what is needed to find treatments that work? Natural products are often effective because they contain multiple compounds working together. It works a bit like tritherapy drugs for AIDS.
Reply | Report Abuse | Link to thisMoreover, we don't need Big Pharma to patent natural products. We need public funding for unpatented medical research.
The natural world does contain untold millions of bioactive compounds. However, the usual approach to drug discovery goes something like this: 1) somebody isolates a few mg of a compound from a plant and disocovers it has some biological activity - there is rarely enough available to test it properly; 2) chemists attempt to synthesise the natural product, this often takes years of work; 3) the resulting array of molecules is tested, if they are too toxic or otherwise not suitable, all this work has effectively been wasted. Also it is often not known how natural products work in the body - much of the complex structure of a natural product can be unecessary or even contribute to side effects or solubility problems.
Reply | Report Abuse | Link to thisRecently a new approach based on detailed biological study has been used - the anti-flu drug relenza was developed specifically to inhibit an enzyme active site on the surface of the flu virus once the structure of both the site and the substate that normally binds there were known by crystallography. With increased biological understanding it makes sense to design drugs by this rational procedure rather than the hit and miss natural product synthesis and testing approach.
I'm not saying that natural products are valueless, and I'm the first to admit that natural biosynthesis processes have a lot to teach us but I think it is inevitable that a drift away from the use of natural products (either isolated or synthetic) as drugs is inevitable and beneficial.
More than half of all drugs are derived from a living organism, yet mankind is destroying the natural world at a stunning rate. I have no doubt the cure to many dreaded diseases exist in Mother nature's pharmacy, but we may lose them before they can be discovered. Also, if the pharma. companies would provide local communities with roaylties this would incentivize nations to preserve their biodiversity. However, I realize this is probably asking too much of capitalism.
Reply | Report Abuse | Link to thisNatural compounds are not necessarily complex. There are quite a number of small molecules. An isolated active compound can be structurally modified so that the new compound may be patented and have higher potency.
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